Disease Creep or Good Medical Practice?

The American Heart Association has been monitoring deaths due to cardiovascular disease (CVD) in the U.S. for over a century. While the CVD death rate grew steadily for most of the 20th century, it leveled off and then began to drop somewhat over the past 25 years. Nevertheless, CVD is still the leading cause of death in the U.S. with 600,000 people dying annually, which accounts for more than 25% of all deaths in the country. The direct costs associated with treating heart disease amount to over $80 billion/year and indirect costs attributed to loss of productivity exceed $60 billion/year.

Despite the progress made in moderating the CVD death rate, it is still a major disease. Furthermore, as the obesity epidemic continues in the U.S., recent headway is liable to be counteracted by the increase in obesity, which is already resulting into a concomitant increase in type 2 diabetes, a precursor to heart disease. Even with improvements in diagnosis and treatment, better understanding of risk factors, reductions in smoking, etc., CVD is going to remain a major health problem for decades.

Diet and exercise are keys to staying healthy, not just to ward off heart disease and diabetes but other diseases as well. Yet, there are times when medical treatment becomes a necessary add-on to preventing heart attacks and strokes. It is not a coincidence that the lowering of CVD deaths occured at the advent of statins such as Zocor (simvastatin) and Lipitor (atorvastatin), drugs that lower LDL cholesterol which is a key factor in the formation of atherosclerosis. These medicines have been shown to be both effective and safe for long-term use.

“Elevated cholesterol is not a disease. It doesn’t cause symptoms. It is a risk factor. People with high cholesterol levels are somewhat more likely to develop a heart attack or stroke, but they are at far less risk than individuals who already have cardiovascular disease. This is the definition of disease creep: when pre-conditions or risk-factors are treated as if they are the same as the actual disease state.”

In Lenzer’s utopia, you wouldn’t get a statin until AFTER you have already had a heart attack. The problem is that many first heart attacks are fatal – you don’t get a second chance to go on statin therapy then. She is correct in saying that just having high cholesterol alone does not justify taking a statin to prevent a heart attack or stroke. But CVD risk factors also include male sex, older age, family history of heart disease, post-menopause, smoking, obesity, high blood pressure, diabetes and stress. If a patient presents to a physician with multiple risk factors and if diet and exercise have not been effective in lowering cholesterol levels to those recommended by the American Heart Association, that physician would be remiss if the patient wasn’t prescribed a statin. Waiting for a patient to first have a heart attack or stroke before providing such treatment would be irresponsible.

Lenzen implies in her article that the prophylactic use of statins may only prevent 1 in 50 heart attacks. I don’t necessarily agree with that number, but let’s say that is correct. There are 785,000 first heart attacks/year in the U.S. Even employing Lenzen’s assumptions, the use of statins in the overall treatment paradigm of patients with multiple CVD risk factors would prevent thousands of heart attacks or strokes annually. Now that the most-studied statins like simvastatin and atorvastatin are generic, it would seem like the cost-benefit of statin use to prevent first heart attacks is non-controversial. This isn’t “Disease Creep” – it is simply good medical practice.

Lenzen is absolutely right about “disease creep”, where we treat risk factors as if they were diseases. But the example of statins is just about the worst possible example.

As you point out, even on Lenzen’s assumptions, statins have saved thousands of lives annually. Clearly, the risk factors that are modulated by statins are causally related to CHD and strokes, and so the risk factor modification you get with statins has clinical benefit.

But there are plenty of examples where this hasn’t proven to be the case. Lowering blood glucose with some agents does not reverse all the harms of diabetes; reducing high blood pressure with some agents does not reverse the harm of hypertension. Increasing HDL with CETP inhibitors doesn’t seem to reduce risk of heart attacks (though the jury is still out on this one). In these cases, the “risk factors” being measured are linked to the disease but are not the cause of the disease, and treating the risk factor is not the same as treating the underlying disease.

So Lenzen is right to caution that we should treat diseases and not risk factors, but dead wrong to suggest that widespread use of statins to lower cholesterol is “disease creep”. I agree with you entirely – its just good evidence-based medicine.

David,
Thanks for your comment. The FDA recognizes that simply addressing a biomarker like blood glucose may not be beneficial in the longterm. Thus, FDA is requiring outcomes studies for drugs to treat diabetes, osteoporosis, etc. I think this is a good thing, but it drives up drug development costs dramatically. The upside is that, if a new drug not only lowers plasma glucose but also reduces diabetic complications, it will be an important new treatment.
– John

You are absolutely right.
What people dont seem to get about statins is that the hundreds of thousands of patients who have been in clinical trials with the drugs have been considered either having good outcomes or placebo type outcomes. Very black and white… and appropriate analysis.

However, the patient who were getting statins for years in these trials and had no heart attacks were not usually followed up to see what happens… and what is probably happening in many of these people is that their plaque has regressed and the benefit of statins persists much longer than the trial observed them.

If you look at teh WOSCOPS trial, you’ll see that ten years after the trial, people still had a lower rate of cororary dealths. In other words, the statin durably mitigated the atherosclerotic process.

Chances are good that half the people in the Western world will get coronary disease. It sure looks like cheap statins can prevent or minimize a whole lot of it, and probably much more than we actually have studied.

did none of you receive the message that statin use was associated with the onset of Type 2 diabetes? In fact, JUPITER noted that for every person who was helped by Crestor (by not suffering an MI) 3/4 of a person developed diabetes. And the decrease in smoking correlates to the decrease in CVD death rates. Why is no one citing this change in behavior related to CVD rates?
pharmacogenetic studies have reported greatly increased plasma statin levels for individuals taking statins who possess 2 specific mutations in the SLCO1B1 gene which codes for a transport protein responsible for movement of statins into liver for Phase !! detoxification, resulting in toxic statin levels.

excerpted pharmacokinetics for atorvastatin:
“The SLCO1B1 genotype was significantly associated with the pharmacokinetics of atorvastatin. In subjects with the variant c.521CC genotype, the mean AUC0-48 of the parent atorvastatin (acid) was 144% (P C SNP were found in America (24%; 95% CI, 18–32%)”https://www.doria.fi/bitstream/handle/10024/42771/pharmaco.pdf

Obviously not rare mutations. So much for the “proven safety” of statins.

[…] which I believe merits a considered response. A couple of weeks ago, I wrote a piece entitled: “Disease Creep or Good Medical Practice?” Essentially, I was challenging the view that the use of statins to lower LDL cholesterol is […]